Non-invasive device and method for the diagnosis of pulmonary vascular occlusions

ABSTRACT

The invention involves a device and method for ascertaining the functioning of the respiratory system and, in particular, for measuring the efficiency of alveolar ventilation of a patient. The device comprises an apparatus containing sensors for measuring the oxygen and carbon dioxide concentrations as well as the volume of air inhaled and exhaled by a patient. The patient is provided a mouthpiece for breathing into and out of the device, which subsequently measures the oxygen and carbon dioxide partial pressures of inhaled and exhaled air. From these measurements, the efficiency of alveolar ventilation during each tidal volume breath may be calculated.

CROSS REFERENCES TO RELATED APPLICATION

The present application is a divisional of Applicant's U.S. applicationSer. No. 10/400,339, filed on Mar. 26, 2003 now abandoned, which is adivisional application of U.S. application Ser. No. 09/965,303, filed onSep. 27, 2001.

BACKGROUND OF THE INVENTION

The present invention relates generally to improvements in technologyused in the field of vascular occlusions of the respiratory system, andmore particularly to non-invasive devices and methods for the diagnosisof a pulmonary embolism and related disorders.

DESCRIPTION OF PRIOR ART

A pulmonary embolism occurs when an embolus becomes lodged in lungarteries, thus blocking blood flow to lung tissue. An embolus is usuallya blood clot, known as a thrombus, but may also comprise fat, amnioticfluid, bone marrow, tumor fragments, or even air bubbles that block ablood vessel. Unless treated promptly, a pulmonary embolism can befatal. In the United States alone, around 600,000 cases occur annually,10 percent of which result in death.

The detection of a pulmonary embolism is extremely difficult becausesigns and symptoms can easily be attributed to other conditions andsymptoms may vary depending on the severity of the occurrence.Frequently, a pulmonary embolism is confused with a heart attack,pneumonia, hyperventilation, congestive heart failure or a panic attack.In other cases, there may be no symptoms at all.

Often, a physician must first eliminate the possibility of other lungdiseases before determining that the symptoms, if any, are caused by apulmonary embolism. Traditional diagnostic methods of testing involveblood tests, chest X-rays, and electrocardiograms. These methods aretypically more effective in ruling out other possible reasons than foractually diagnosing a pulmonary embolism. For example, a chest x-ray mayreveal subtle changes in the blood vessel patterns after an embolism andsigns of pulmonary infarction. However, chest x-rays often show normallungs even when an embolism is present, and even when the x-rays showabnormalities they rarely confirm a pulmonary embolism. Similarly, anelectrocardiogram may show abnormalities, but it is only useful inestablishing the possibility of a pulmonary embolism.

As a pulmonary embolism alters the ability of the lungs to oxygenate theblood and to remove carbon dioxide from the blood, one method ofdiagnosing the condition involves taking a specimen of arterial bloodand measuring the partial pressure of oxygen and carbon dioxide in thearterial blood (i.e., an arterial blood gas analysis). Although apulmonary embolism usually causes abnormalities in these measurements,there is no individual finding or combination of findings from thearterial blood gas analysis that allows either a reliable way to excludeor specific way of diagnosing pulmonary embolism. In particular, atleast 15–20% of patients with a documented pulmonary embolism havenormal oxygen and carbon dioxide contents of the arterial blood.Accordingly, the arterial blood analysis cannot reliably include orexclude the diagnosis of a pulmonary embolism.

The blood D-dimer assay is another diagnostic method that has becomeavailable for commercial use. The D-dimer protein fragment is formedwhen fibrin is cleaved by plasmin and therefore produced naturallywhenever clots form in the body. As a result, the D-dimer assay isextremely sensitive for the presence of a pulmonary embolism but is verynonspecific. In other words, if the D-dimer assay is normal, theclinician has a reasonably high degree of certainty that no pulmonaryembolism is present. However, many studies have shown a D-dimer assay isonly normal in less than ⅓ of patients and thus produces a high degreeof false positives. As a result, the D-dimer assay does not obviateformal pulmonary vascular imaging in most patients with symptoms of apulmonary embolism.

In an attempt to increase the accuracy of diagnostic, physicians haverecently turned to methods which can produce an image of a potentiallyafflicted lung. One such method is a nuclear perfusion study whichinvolves the injection of a small amount of radioactive particles into avein. The radioactive particles then travel to the lungs where theyhighlight the perfusion of blood in the lung based upon whether they canpenetrate a given area of the lung. While normal results can indicatethat a patient lacks a pulmonary embolism, an abnormal scan does notnecessarily mean that a pulmonary embolism is present. Nuclear perfusionis often performed in conjunction with a lung ventilation scan tooptimize results.

During a lung ventilation scan, the patient inhales a gaseousradioactive material. The radioactive material becomes distributedthroughout the lung's small air sacs, known as alveoli, and can beimaged. By comparing this scan to the blood supply depicted in theperfusion scan, a physician may be able to determine whether the personhas a pulmonary embolism based upon areas that show normal ventilationbut lack sufficient perfusion. Nevertheless, a perfusion scan does notalways provide clear evidence that a pulmonary embolism is the cause ofthe problem as it often yields indeterminate results in as many as 70%of patients.

Pulmonary angiograms are popular means of diagnosing a pulmonaryembolism, but the procedure poses some risks and is more uncomfortablethan other tests. During a pulmonary angiogram, a catheter is threadedinto the pulmonary artery so that iodine dye can be injected into thebloodstream. The dye flows into the regions of the lung and is imagedusing x-ray technology, which would indicate a pulmonary embolism as ablockage of flow in an artery. Pulmonary angiograms are more useful indiagnosing a pulmonary embolism than some of the other traditionalmethods, but often present health risks and can be expensive. Althoughfrequently recommended by experts, few physicians and patients arewilling to undergo such an invasive procedure.

Spiral volumetric computed tomography is another diagnostic tool thathas recently been proposed as a less invasive test which can delivermore accurate results. The procedure's reported sensitivity has variedwidely, however, and it may only be useful for diagnosing an embolism incentral pulmonary arteries as it is relatively insensitive to clots inmore remote regions of the lungs.

These pulmonary vascular imaging tests have several disadvantages incommon. Nearly all require ionizing radiation and invasiveness of, at aminimum, an intravenous catheter. The imaging tests also typicallyinvolve costs of more than $1,000 for the patient, take more than twohours to perform, and require special expertise such as a trainedtechnician to perform the tests and acquire the images and aboard-certified radiologist to interpret the images. Notably, none arecompletely safe for patients who are pregnant. As a result of theseshortcomings, the imaging procedures are not available in manyoutpatient clinic settings and in many portions of third worldcountries.

Objects and Advantages

It is a principal object and advantage of the present invention toprovide physicians with an instrument for non-invasively diagnosingpulmonary vascular occlusions.

It is an additional object and advantage of the present invention toprovide physicians with an instrument that accurately diagnosespulmonary vascular occlusions.

It is a further object and advantage of the present invention to providean instrument for measuring and interpreting pulmonary test data.

Other objects and advantages of the present invention will in part beobvious, and in part appear hereinafter.

SUMMARY OF THE INVENTION

In accordance with the foregoing objects and advantages, the presentinvention provides a device and method for non-invasively diagnosing apulmonary embolism. The device of the present invention comprises abreathing tube having sensors for measuring the flow of air into and outof a patient's lungs while a remote data processing unit interconnectedto the breathing tube simultaneously determines the oxygen and carbondioxide concentrations. The device further includes a display screen forvisually graphing the resulting calculations and providing a visualmeans for determining the likelihood that a pulmonary embolism ispresent based upon a change in measured gas concentrations.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a respiratory system during inhalation.

FIG. 2 is an illustration of a respiratory system during exhalation.

FIG. 3 is an illustration of a respiratory system afflicted with apulmonary vascular occlusion during exhalation.

FIG. 4 is a schematic representation of the system of the presentinvention.

FIG. 5 is a perspective view of an attachment to the invention.

FIG. 6 is an illustration of a display screen readout.

DETAILED DESCRIPTION

Referring now to the drawing in which like reference numerals refer tolike parts throughout, there is seen in FIG. 1 a representation of lungs10 free from any pulmonary occlusions. In healthy lungs 10, blood flowsfreely from the pulmonary arteries 12 into the capillaries 14surrounding the individual alveoli 16 of the lungs 10. When inhaled air18 is drawn into the lungs 10 and alveoli 16, oxygen is transferred fromthe inhaled air 18 to the blood stream and carbon dioxide is transferredout. Inhaled air 18 typically contains an oxygen partial pressure ofapproximately one hundred (100) torr and a carbon dioxide partialpressure of zero (0) torr.

Once the inhaled air 18 reaches the alveoli 16, the oxygen contentdecreases while the carbon dioxide content increases until anequilibrium with blood gas levels in the pulmonary arteries 12 isreached. The inhaled air 18 is then, as seen in FIG. 2, expired asexhaled air 20. Exhaled air 20 from properly functioning lungs typicallycontains a partial pressure of oxygen of about eighty (80) torr and apartial pressure of carbon dioxide of about forty (40) torr.

FIG. 3 depicts the functioning of a respiratory system afflicted with apulmonary embolism 22 which, as an example, occludes blood flow to anafflicted lung 24. As a result, there is a reduction in the number ofalveoli 16 that participate in gas exchange. This volume of spaceavailable in the alveoli 16 that is lost from participation is commonlyreferred to as alveolar deadspace. Due to the deadspace and loss oftotal alveolar volume available for gas exchange, afflicted lung 24 doesnot exchange gases as readily as the healthy lung 10. Accordingly,exhaled air 26 contains a higher partial pressure of oxygen and lowerpartial pressure of carbon dioxide than air exhaled from a healthy lung.In the example depicted in FIG. 3, exhaled air 26 exiting therespiratory system contains a partial pressure of oxygen of abouteighty-five (85) torr and a partial pressure of carbon dioxide of abouttwenty (20) torr. Thus, the ratio of carbon dioxide to oxygen in exhaledair 26 from afflicted lung 24 (i.e., 20:85) is smaller than the ratio inexhaled air 20 from healthy lung 10 (i.e., 40:80) as seen in FIG. 2.

As seen in FIG. 4, a system 28 for measuring and diagnosing pulmonarydisorders comprises a measuring unit 30 in combination with a dataprocessing unit 50 and a display screen 60. Measuring unit 30 determinesthe overall flow of air inhaled into and exhaled out of the lungs whilesimultaneously determining the partial pressure of oxygen and carbondioxide. Data processing unit 50 computes the concentrations of carbondioxide, oxygen, and nitrogen from the partial pressures and determinesthe ratio of carbon dioxide to oxygen from the raw data obtained bymeasuring unit 30. The ratio of carbon dioxide to oxygen is then plottedagainst expired volume on display screen 60. By comparing the carbondioxide ratios to average readings, the likelihood that a given patienthas a pulmonary embolism can be determined.

Measuring unit 30 comprises a patient mouthpiece 32 connected in fluidcommunication to a breathing tube 34 having an open end 42 through whichair can be inhaled or exhaled. Measuring unit 30 further comprises threesensors; a pneumotach 36, a capnometer 38, and an oxygen monitor 40. Thethree sensors are situated in series and in-line with breathing tube 34for simultaneously measuring the flow, carbon dioxide, and oxygen levelsof inhaled and exhaled air. Infrared and paramagnetic type sensors arepreferred respectively. Sensors using spectrometric techniques may alsowork for both oxygen and carbon dioxide measurements providing they cansupply data with rapid enough response time for breath-to-breath,real-time plotting. The mainstream technique for measuring the inhaledor exhaled air is preferred, but the sidestream technique may also beeffective.

As seen in FIG. 5, a T-piece adaptor 70 may optionally be provided atopen end 42 of breathing tube 34 for use with patients that are oxygendependant. T-piece adapter 70 contains an inlet valve 72 and an outletvalve 74 which properly direct the passage of inhaled and exhaled airthrough the breathing tube 34. By connecting an oxygen dependantpatient's supply to the intake valve 72, inhaled air can first be passedthrough the three sensors 36, 38, 40 to establish baseline readings ofthe oxygen and carbon dioxide concentrations for comparison to exhaledair, since an oxygen dependent patient receives air that has differentconcentrations than present in ambient air.

Data processing unit 50 comprises a commercially available computerprocessor programmed with software for the interpretation of the dataobtained from measuring unit 30 and background comparison data. Softwarecan be specifically developed to perform the necessary calculations todetermine the partial pressures and carbon dioxide to oxygen ratios orsoftware can optionally be purchased commercially and, if necessary,modified to run the appropriate algorithms. After additional research,the background comparison data can be updated based on data obtainedfrom use of the invention to further refine expected normal values.

Display screen 60 comprises a cathode ray tube, plasma screen, or othervisual display for displaying computerized data. Screen 60 canoptionally display graphs representing predetermined reference orbackground data for test populations against which the current readingscan be plotted for a visual comparison. In addition to displaying thecarbon dioxide to oxygen ratios as a function of time calculated by dataprocessing unit 50, screen 60 may optionally display a plot of theexpired oxygen and carbon dioxide partial pressures. Using this display,a physician may estimate the efficiency of alveolar ventilation inpatients with acute respiratory distress syndromes to assist in decidingthe mechanical ventilation settings.

In addition to the three primary sensors 36, 38, 40, data processingunit 50 may optionally be connected to a pulse oximeter 44 that measuresarterial oxygen saturation of hemoglobin in the arterial blood. Fromthese data, and the additional measurement of pH and hemoglobinconcentration in a peripheral venous blood sample, the cardiac output ofthe patient can be calculated according to the Fick equation. In orderto perform the Fick equation, the average total oxygen consumed, thearterial oxygen content and venous oxygen content must be determined.The average total oxygen consumed can be determined from the oxygentension and flow curves over a predetermined time period. For thepurposes of determining cardiac output, a one minute time period issufficient. The arterial oxygen content can be estimated by multiplyingthe arterial oxygen saturation (measured by pulse oximeter 44) by thehemoglobin concentration (determined from the venous blood sample). Thevenous oxygen content can be calculated by mathematical manipulation ofthe nadir (mean lowest) oxygen tension measured during deep expiration(in an awake patient) or a sign exhalation (in a mechanically ventilatedpatient) over the predetermined time period. From the nadir oxygentension, venous oxygen saturation can be estimated according topublished oxygen binding curves for the measured pH. The venous oxygencontent is then calculated by multiplying the venous oxygen saturationby the venous hemoglobin (measured from the venous blood sample). Oncethese calculations have been made, the cardiac output is determined bydividing the total oxygen consumed by the difference between thearterial oxygen content and the venous oxygen content. The algorithm forthe Fick calculation can be programmed into the data processing unitsoftware and the results displayed on screen 60. The cardiac outputmeasurement is useful for assisting the physician in determining thesuccess or failure of treatment designed to relieve pulmonary vascularobstructions, or to treat circulatory shock.

Device 28 is used by having a patient breathe (inhale and exhale apredetermined number of times in succession) through mouthpiece 32 ofthe measuring unit 30. As the patient inhales and exhales the pneumotachflow sensor 36, capnometer 38, and oxygen monitor 40 perform theirrespective readings, which are then electrically transmitted via wiresor cabling to data processing unit 50. The programmable software loadedinto data processing unit 50 convert the measurements into volume andconcentration readings, calculate the carbon dioxide to oxygen ratio,and display this ratio on screen 60 in the form of a graph against thevolume of air expired. Readings may be optimized by requiring thepatient to hold in inhaled air for several heartbeats before exhalingthrough the mouthpiece 32 of the measuring unit 30. It has beendetermined through testing that patients without a pulmonary embolismwill normally have a carbon dioxide to oxygen ratio of 0.30 or greaterwhile patients with a pulmonary embolism will have a carbon dioxide tooxygen ratio of 0.25 or less.

Device 28 may also be used for the detection of whole-body oxygenconsumption and determination of the adequacy of oxygen delivery duringresuscitation from shock. During conditions of systemic inflammation thebody will extract oxygen at higher levels than normal, resulting in anincrease in the partial pressure of carbon dioxide-to-oxygen ratio inexhaled air. By using T-piece 70 in the manner explained above, theconcentration of the oxygen provided to the patient and theconcentration of the oxygen exhaled can be determined. As illustrated inFIG. 6, when the level of oxygen delivery (i.e., the amount providedminus the amount exhaled) observed at two inspired oxygen concentrationsreaches normal levels a physician has visual conformation that theresuscitation performed is adequate. One method of determining theadequacy of resuscitation is to determine oxygen delivery at bothrelatively low fixed concentrations of oxygen and at relatively highfixed concentration. Relatively low concentrations include from abouttwenty-one to thirty percent (21–30%) oxygen and relatively high oxygenconcentrations involve about forty-five to one hundred percent (45–100%)oxygen. The difference between oxygen delivery at relatively lowconcentrations verses relatively high concentrations can be comparedagainst a nomogram for healthy patients of similar age, body mass, bodymass index, and gender and used to assess the adequacy of fluid andvasopressor resuscitation.

Data processing unit 50 can additionally be programmed to display onscreen 60 any of the individual measurements taken by sensors 36, 38,40, and 44, or combinations thereof for diagnostic purposes. Forexample, a plot of the expired carbon dioxide and oxygen concentrationover time could be used to estimate the efficiency of alveolarventilation in patients with acute respiratory distress syndrome.Additionally, the plotted data from sensors 36, 38, 40, and 44 could beused to assist in deciding how to properly adjust mechanical ventilatorssetting, such as the degree of positive end-expiratory pressure, minuteventilation, and peak inspiratory pressure settings, to optimize patientcare. For example, data from sensors 36, 37, 40, and 44, can be plottedindividually in patients who are being mechanically ventilated. Bysimultaneously plotting the partial pressures of oxygen and carbondioxide as a function of volume of each breath, the amount of carbondioxide released and percentage of oxygen extracted can be determined.If the barometric pressure is known or inputted into data processingunit 50, the efficiency of alveolar ventilation during each tidal volumebreath can be calculated. This information can then be used to adjustmechanical ventilation to optimize alveolar efficiency or breathingalveolar ventilation efficiency.

1. A method of measuring the efficiency of alveolar ventilation,comprising the steps of: providing a mouthpiece to a patient; allowingsaid patient to inhale and exhale through said mouthpiece; measuring theoxygen and carbon dioxide partial pressures of inhaled air; measuringthe oxygen and carbon dioxide partial pressures of the exhaled air; andestimating the efficiency of alveolar ventilation during each tidalvolume breath.
 2. The method of claim 1, further comprising the step ofdisplaying a plot of the expired oxygen and carbon dioxide partialpressures prior to said step of estimating the efficiency of alveolarventilation.
 3. The method of claim 2, wherein the oxygen and carbondioxide partial pressures of inhaled and exhaled air are measured by anoxygen monitor in fluid communication with said breathing tube.
 4. Themethod of claim 2, wherein the carbon dioxide partial pressures of saidinhaled and exhaled air are measured by a capnometer in fluidcommunication with said breathing tube.
 5. The method of claim 1,further comprising the step of adjusting the pressure and volumeparameters of a mechanical ventilator based on said estimation of theefficiency of alveolar ventilation.
 6. The method of claim 1, whereinthe step of estimating the efficiency of alveolar ventilation comprisesthe steps of: determining the amount of carbon dioxide released from thepatient, determining the percentage of oxygen extracted by the patient;and calculating the efficiency of alveolar ventilation from said amountof carbon dioxide released from the patient and said percentage ofoxygen extracted by the patient.
 7. The method of claim 6, furthercomprising the step of determining the barometric pressure.